Regulatory mechanisms controlling human E-cadherin gene expression

Yan Nan Liu, Wen Wen Lee, Chun Yi Wang, Tung Hui Chao, Yvan Chen, Hshiung Chen Ji

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

In cancer cells, loss of E-cadherin gene expression caused dysfunction of the cell-cell junction system, triggering cancer invasion and metastasis. Therefore, E-cadherin is an important tumor-suppressor gene. To understand how E-cadherin gene expression is regulated in cancer cells, we have used E-cadherin-positive and -negative expressing cells to find out the possible up- or downregulating transcription factors in human E-cadherin regulatory sequences. Functional analysis of human E-cadherin regulatory sequences constructs indicated that AML1, Sp1, and p300 may play important roles in promoting E-cadherin expression. In addition, we found there are four HNF3-binding sites in human E-cadherin regulatory sequences. The exogenous HNF3 can enhance the E-cadherin promoter activity in metastatic breast cancer cells and the metastatic breast cancer cells stably transfected with HNF3 showed re-expression of E-cadherin. The HNF3 stable transfectants changed from mesenchymal-like into epithelial morphology. The trans-well assays showed the re-expressed E-cadherin reduced cell motility of metastatic breast cancer cells. These results suggested HNF3 may play important roles in the upregulation of the E-cadherin promoter, with the consequent re-expression of E-cadherin, thus reducing the metastatic potential of breast cancer cells. These findings suggested HNF3 plays important roles in the upregulation of the E-cadherin gene and may be able to reduce the motility of metastatic breast cancer cells.

Original languageEnglish
Pages (from-to)8277-8290
Number of pages14
JournalOncogene
Volume24
Issue number56
DOIs
Publication statusPublished - Dec 15 2005
Externally publishedYes

Keywords

  • E-cadherin
  • Gene expression
  • HNF3 (Hepatocyte Nuclear Factor)
  • Metastasis

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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  • Cite this

    Liu, Y. N., Lee, W. W., Wang, C. Y., Chao, T. H., Chen, Y., & Ji, H. C. (2005). Regulatory mechanisms controlling human E-cadherin gene expression. Oncogene, 24(56), 8277-8290. https://doi.org/10.1038/sj.onc.1208991